Severe acute respiratory syndrome coronavirus spike glycoprotein (S protein) (Spike (S) glycoprotein)

The spike (S) glycoprotein is the major surface protein of coronaviruses, forming homotrimers that protrude from the virion and mediate attachment to host receptors and fusion of viral and cellular membranes, thereby enabling viral entry into cells[4]. Each protomer of the SARS‑CoV‑2 spike is a single-pass type I transmembrane glycoprotein of 1,273 amino acids with a large N‑terminal ectodomain and a short C‑terminal cytoplasmic tail; the trimer is heavily glycosylated[6][4]. The S protein is a class I viral fusion protein composed of two functional subunits: S1, which contains the receptor-binding domain (RBD) that binds the host receptor angiotensin‑converting enzyme 2 (ACE2), and S2, which contains the fusion peptide, heptad repeats (HR1/HR2), transmembrane domain, and cytoplasmic tail that drive membrane fusion[6][3]. SARS‑CoV‑2 spike binds human ACE2 with affinity comparable to SARS‑CoV and contains a distinctive multibasic furin cleavage site at the S1/S2 boundary that is processed during biogenesis and primes the protein for entry[7][1][9]. Structural studies have resolved prefusion and postfusion conformations and documented RBD “up/down” states and ACE2-bound complexes, providing a blueprint for vaccines and entry inhibitors[1][10][3]. The S glycoprotein is the principal target of neutralizing antibodies after infection or vaccination and is therefore a key therapeutic and vaccine antigen; changes in spike, such as D614G and other variant mutations, modulate infectivity, fusion, and antibody sensitivity[5][8][7].

Other names

Spike proteinS glycoproteinSARS-CoV spike glycoproteinSARS-CoV-2 spike glycoproteinCoronavirus spike proteinS protein trimerPeplomer

Neutralizing antibodies bind the receptor-binding domain (RBD) in S1 to block ACE2 engagement and prevent attachment/entry Antibodies bind non-RBD epitopes (e.g., NTD “supersite,” S2 epitopes) to neutralize and/or inhibit conformational changes needed for fusion Soluble ACE2 or ACE2-mimetics compete with cellular ACE2 for RBD binding Protease inhibitors targeting host proteases (e.g., TMPRSS2, metalloproteases) reduce S activation and S-mediated cell–cell fusion HR1/HR2 peptide mimetics disrupt six-helix bundle formation in S2, blocking membrane fusion Vaccines induce anti-spike neutralizing antibodies and T-cell responses that block infection or reduce disease severity